On the Nature of Improper Hydrogen Bonding in RCH 2 F and RCHF 2 Motifs

Abstract The RCH 2 F and RCHF 2 groups are substituents of interest in medicinal and agrochemicals products. They have a polar aspect relative to the methyl (RCH 3 ) or trifluoromethyl (RCF 3 ) groups which results in a lowering of Log P's (water affinity). Here we use a computational approach to explore the nature of the interaction between RCH 2 F and RCHF 2 in methanes and ethanes with chloride ion (and water), as a hydrogen bonding acceptor. A key observation is that the hydrogen atoms geminal to the fluorine(s) become less positively charged with increasing fluorination, a trend anticipated to weaken, not strengthen, their hydrogen bonding interactions. However this study demonstrates a dominating role for the electrostatic interaction of the acceptor with the CF carbons and profiles a shift in negative charge density from hydrogen to the carbon and fluorine(s) as chloride ion (or water) approach. The common occurrence of blue shifts (shortening C─H length) in these ‘improper’ or ‘non‐classical’ hydrogen bonds is also explored and is correlated with the electrostatic interactions between the acceptor and the carbon atoms. These observations are extended to C 3 ─C 6 alicyclic rings containing these motifs and predict particularly strong interactions energies between chloride ion and specifically designed organo‐fluoro alicycles.